Tom 3, Nr 3-4 (2023)
Wytyczne / stanowisko ekspertów
Opublikowany online: 2023-08-29
Standaryzacja wielokolorowej cytometrii przepływowej w diagnostyce ostrych białaczek limfoblastycznych u dzieci — wytyczne grupy AIEOP-BFM
1, 1
DOI: 10.5603/hemedu.95478
Hematologia — Edukacja 2023;3(3-4):104-117.
Streszczenie
Immunofenotypowanie za pomocą cytometrii przepływowej (FCM) jest obecnie jedną z podstawowych metod diagnostycznych w rozpoznawaniu ostrych białaczek. Jednakże wieloośrodkowe dane pokazują pewne braki i niespójności między obowiązującymi klasyfikacjami, standaryzacją technologiczną a ich wdrożeniem do praktyki klinicznej. Grupa Associazone Italiana Ematologia Oncologia Pediatrica-Berlin–Frankfurt–Münster, w skład której wchodziło 9 europejskich ośrodków referencyjnych w diagnostyce immunofenotypowej białaczek u dzieci, opracowała wytyczne mające na celu walidację i standaryzację samej metody oraz — co ważniejsze — wypracowała również wspólne wytyczne opisujące wdrożenie możliwości wielokolorowej FCM do praktyki klinicznej. Przedstawiono wymagania dotyczące panelu diagnostycznego, systemu bramkowania blastów, kontroli wewnętrznej, trójstopniowej oceny ekspresji antygenów, opisu heterogenności komórek blastycznych i tworzenia subklonów, dopracowano immunologiczny system klasyfikacji ostrych białaczek limfoblastycznych oraz algorytm postępowania w ocenie linii dominującej w przypadkach białaczek dwuliniowych lub ze złożonym immunofenotypem, co ma decydujące znaczenie w doborze odpowiedniego leczenia. Niniejsze wytyczne są ważnym krokiem w kierunku niezbędnej standaryzacji międzylaboratoryjnej diagnostyki immunofenotypowej białaczek u dzieci, stosunkowo łatwym do wdrożenia w laboratoriach diagnostycznych oraz ułatwiającym prowadzenie wieloośrodkowych badań klinicznych. Celem niniejszej pracy jest rozpowszechnienie w Polsce przedstawionych wytycznych. Umożliwi to sprawniejsze porównywanie wyników między ośrodkami oraz ułatwi ich interpretację przez lekarzy klinicystów w sytuacjach wieloośrodkowej opieki nad pacjentem, na przykład w jednostkach diagnostycznej, leczniczej i transplantacyjnej.
Słowa kluczowe: standaryzacjacytometria przepływowaimmunofenotypowanieostra białaczka limfoblastyczna u dzieci
Artykuł dostępny w formacie PDF
Pokaż PDFReferencje
- Dworzak MN, Buldini B, Gaipa G, et al. International-BFM-FLOW-network. AIEOP-BFM consensus guidelines 2016 for flow cytometric immunophenotyping of Pediatric acute lymphoblastic leukemia. Cytometry B Clin Cytom. 2018; 94(1): 82–93.
- Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022; 36(7): 1703–1719.
- Alaggio R, Amador C, Anagnostopoulos I, et al. International Agency for Research on Cancer/World Health Organization. Correction: "The 5th edition of The World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms" Leukemia. 2022 Jul;36(7):1720-1748. Leukemia. 2023; 37(9): 1944–1951.
- Basso G, Buldini B, De Zen L, et al. New methodologic approaches for immunophenotyping acute leukemias. Haematologica. 2001; 86(7): 675–692.
- Wood BL, Arroz M, Barnett D, et al. 2006 Bethesda International Consensus recommendations on the immunophenotypic analysis of hematolymphoid neoplasia by flow cytometry: optimal reagents and reporting for the flow cytometric diagnosis of hematopoietic neoplasia. Cytometry B Clin Cytom. 2007; 72(Suppl 1): S14–S22.
- Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114(5): 937–951.
- Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20): 2391–2405.
- Béné MC, Nebe T, Bettelheim P, et al. Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10. Leukemia. 2011; 25(4): 567–574.
- van Dongen JJM, Lhermitte L, Böttcher S, et al. EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708). EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012; 26(9): 1908–1975.
- Kalina T, Flores-Montero J, van der Velden VHJ, et al. EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708). EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols. Leukemia. 2012; 26(9): 1986–2010.
- van der Does-van den Berg A, Bartram CR, Basso G, et al. Minimal requirements for the diagnosis, classification, and evaluation of the treatment of childhood acute lymphoblastic leukemia (ALL) in the "BFM Family" Cooperative Group. Med Pediatr Oncol. 1992; 20(6): 497–505.
- Béné MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995; 9(10): 1783–1786.
- Béné MC, Bernier M, Casasnovas RO, et al. The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. Blood. 1998; 92(2): 596–599.
- Ratei R, Karawajew L, Lacombe F, et al. European Working Group of Clinical Cell Analysis (EWGCCA). Normal lymphocytes from leukemic samples as an internal quality control for fluorescence intensity in immunophenotyping of acute leukemias. Cytometry B Clin Cytom. 2006; 70(1): 1–9.
- Coustan-Smith E, Mullighan CG, Onciu M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009; 10(2): 147–156.
- Attarbaschi A, Mann G, König M, et al. Mixed lineage leukemia-rearranged childhood pro-B and CD10-negative pre-B acute lymphoblastic leukemia constitute a distinct clinical entity. Clin Cancer Res. 2006; 12(10): 2988–2994.
- Mullighan CG, Collins-Underwood JR, Phillips LAA, et al. Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat Genet. 2009; 41(11): 1243–1246.
- Zangrando A, Intini F, te Kronnie G, et al. Validation of NG2 antigen in identifying BP-ALL patients with MLL rearrangements using qualitative and quantitative flow cytometry: a prospective study. Leukemia. 2008; 22(4): 858–861.
- Borowitz MJ, Bene M-C, Harris NL, Porwit A, Matutes E. Acute leukaemias of ambiguous lineage. In: Swerdlow S, Campo E, Harris NL. et al. ed. WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon 2008: 149–155.
- Rubnitz JE, Onciu M, Pounds S, et al. Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital. Blood. 2009; 113(21): 5083–5089.
- Al-Seraihy AS, Owaidah TM, Ayas M, et al. Clinical characteristics and outcome of children with biphenotypic acute leukemia. Haematologica. 2009; 94(12): 1682–1690.
- Gerr H, Zimmermann M, Schrappe M, et al. Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations. Br J Haematol. 2010; 149(1): 84–92.
- Mejstrikova E, Volejnikova J, Fronkova E, et al. Prognosis of children with mixed phenotype acute leukemia treated on the basis of consistent immunophenotypic criteria. Haematologica. 2010; 95(6): 928–935.
- Steiner M, Attarbaschi A, Dworzak M, et al. Austrian Berlin-Frankfurt-Münster Study Group. Cytochemically myeloperoxidase positive childhood acute leukemia with lymphoblastic morphology treated as lymphoblastic leukemia. J Pediatr Hematol Oncol. 2010; 32(1): e4–e7.
- Matutes E, Pickl WF, Van't Veer M, et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood. 2011; 117(11): 3163–3171.
- Weinberg OK, Arber DA. Mixed-phenotype acute leukemia: historical overview and a new definition. Leukemia. 2010; 24(11): 1844–1851.
- Borowitz MJ, Borowitz MJ. Mixed phenotype acute leukemia. Cytometry B Clin Cytom. 2013 [Epub ahead of print]; 86(3): 152–153.
- Inukai T, Kiyokawa N, Campana D, et al. Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15. Br J Haematol. 2012; 156(3): 358–365.
- Zhang J, Ding Li, Holmfeldt L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012; 481(7380): 157–163.
- Dworzak MN, Gaipa G, Ratei R, et al. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: Multicentric assessment is feasible. Cytometry B Clin Cytom. 2008; 74(6): 331–340.
- Karawajew L, Dworzak M, Ratei R, et al. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia. Haematologica. 2015; 100(7): 935–944.
- Veltroni M, De Zen L, Sanzari MC, et al. I-BFM-ALL-FCM-MRD-Study Group. Expression of CD58 in normal, regenerating and leukemic bone marrow B cells: implications for the detection of minimal residual disease in acute lymphocytic leukemia. Haematologica. 2003; 88(11): 1245–1252.
- Mazumder S, Manivannan P, Bhandary C, et al. Proposed single-tube ten-color antibody panel to optimize resources for measurable residual disease detection in b-acute lymphoblastic leukemia based on leukemia associated immunophenotype evaluation at diagnosis: a single center experience from southern india. J Leuk. 2022; 10: 308.
- Płotka A, Lewandowski K. BCR/ABL1-Like acute lymphoblastic leukemia: from diagnostic approaches to molecularly targeted therapy. Acta Haematol. 2022; 145(2): 122–131.
- Djokic M, Björklund E, Blennow E, et al. Overexpression of CD123 correlates with the hyperdiploid genotype in acute lymphoblastic leukemia. Haematologica. 2009; 94(7): 1016–1019.
- Kalina T, Vaskova M, Mejstrikova E, et al. Myeloid antigens in childhood lymphoblastic leukemia: clinical data point to regulation of CD66c distinct from other myeloid antigens. BMC Cancer. 2005; 5: 38.
- Hrusák O, Porwit-MacDonald A. Antigen expression patterns reflecting genotype of acute leukemias. Leukemia. 2002; 16(7): 1233–1258.
- De Zen L, Orfao A, Cazzaniga G, et al. Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia: correlation with specific genotype. I. ETV6/AML1 ALLs identification. Leukemia. 2000; 14(7): 1225–1231.
- Bugarin C, Sarno J, Palmi C, et al. I-BFM study group. Fine tuning of surface CRLF2 expression and its associated signaling profile in childhood B-cell precursor acute lymphoblastic leukemia. Haematologica. 2015; 100(6): e229–e232.
- Morak M, Attarbaschi A, Fischer S, et al. Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2-harboring clones as main relapse-driving force in childhood ALL. Blood. 2012; 120(26): 5134–5142.
- Attarbaschi A, Morak M, Cario G, et al. Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-Berlin-Frankfurt-Münster (BFM) Study Group and National Cancer Research Institute (NCRI)-Children's Cancer and Leukaemia (CCLG) Study Group. Treatment outcome of CRLF2-rearranged childhood acute lymphoblastic leukaemia: a comparative analysis of the AIEOP-BFM and UK NCRI-CCLG study groups. Br J Haematol. 2012; 158(6): 772–777.
- Vaskova M, Mejstrikova E, Kalina T, et al. Transfer of genomics information to flow cytometry: expression of CD27 and CD44 discriminates subtypes of acute lymphoblastic leukemia. Leukemia. 2005; 19(5): 876–878.
- Attarbaschi A, Mann G, Schumich A, et al. CD44 deficiency is a consistent finding in childhood Burkitt's lymphoma and leukemia. Leukemia. 2007; 21(5): 1110–1113.
- Schinnerl D, Mejstrikova E, Schumich A, et al. CD371 cell surface expression: a unique feature of -rearranged acute lymphoblastic leukemia. Haematologica. 2019; 104(8): e352–e355.
- Slamova L, Starkova J, Fronkova E, et al. CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. Leukemia. 2014; 28(3): 609–620.
- Lanza F, Latorraca A, Moretti S, et al. Comparative analysis of different permeabilization methods for the flow cytometry measurement of cytoplasmic myeloperoxidase and lysozyme in normal and leukemic cells. Cytometry. 1997; 30(3): 134–144.
- Kappelmayer J, Gratama JW, Karászi E, et al. Flow cytometric detection of intracellular myeloperoxidase, CD3 and CD79a. Interaction between monoclonal antibody clones, fluorochromes and sample preparation protocols. J Immunol Methods. 2000; 242(1-2): 53–65.
- Wood B, Jevremovic D, Béné MC, et al. ICSH/ICCS Working Group. Validation of cell-based fluorescence assays: practice guidelines from the ICSH and ICCS - part V - assay performance criteria. Cytometry B Clin Cytom. 2013; 84(5): 315–323.
- Johansson U, Bloxham D, Couzens S, et al. British Committee for Standards in Haematology. Guidelines on the use of multicolour flow cytometry in the diagnosis of haematological neoplasms. British Committee for Standards in Haematology. Br J Haematol. 2014; 165(4): 455–488.
- Owens MA, Vall HG, Hurley AA, et al. Validation and quality control of immunophenotyping in clinical flow cytometry. J Immunol Methods. 2000; 243(1-2): 33–50.
- Arnoulet C, Béné MC, Durrieu F, et al. Four- and five-color flow cytometry analysis of leukocyte differentiation pathways in normal bone marrow: a reference document based on a systematic approach by the GTLLF and GEIL. Cytometry B Clin Cytom. 2010; 78(1): 4–10.
- Mahnke YD, Roederer M. Optimizing a multicolor immunophenotyping assay. Clin Lab Med. 2007; 27(3): 469–85, v.
- Hulspas R, O'Gorman MRG, Wood BL, et al. Considerations for the control of background fluorescence in clinical flow cytometry. Cytometry B Clin Cytom. 2009; 76(6): 355–364.
- Tangri S, Vall H, Kaplan D, et al. ICSH/ICCS Working Group. Validation of cell-based fluorescence assays: practice guidelines from the ICSH and ICCS — part III — analytical issues. Cytometry B Clin Cytom. 2013; 84(5): 291–308.
- Del Vecchio L, Brando B, Lanza F, et al. Italian Society for Cytometry. Recommended reporting format for flow cytometry diagnosis of acute leukemia. Haematologica. 2004; 89(5): 594–598.
- Gratama JW, D'hautcourt JL, Mandy F, et al. Flow cytometric quantitation of immunofluorescence intensity: Problems and perspectives. Cytometry. 1998; 33(2): 166–178, doi: 10.1002/(sici)1097-0320(19981001)33:2<166::aid-cyto11>3.0.co;2-s.
- Lenkei R, Gratama JW, Rothe G, et al. Performance of calibration standards for antigen quantitation with flow cytometry. Cytometry. 1998; 33(2): 188–196, doi: 10.1002/(sici)1097-0320(19981001)33:2<188::aid-cyto13>3.0.co;2-q.
- Hrušák O, Basso G, Ratei R, et al. AIEOP-BFM Flow Network. Flow diagnostics essential code: a simple and brief format for the summary of leukemia phenotyping. Cytometry B Clin Cytom. 2014; 86(4): 288–291.
- Ratei R, Schabath R, Karawajew L, et al. Lineage classification of childhood acute lymphoblastic leukemia according to the EGIL recommendations: results of the ALL-BFM 2000 trial. Klin Padiatr. 2013; 225(Suppl 1): S34–S39.
- Kansal R, Deeb G, Barcos M, et al. Precursor B lymphoblastic leukemia with surface light chain immunoglobulin restriction: a report of 15 patients. Am J Clin Pathol. 2004; 121(4): 512–525.
- Li S, Lew G. Is B-lineage acute lymphoblastic leukemia with a mature phenotype and l1 morphology a precursor B-lymphoblastic leukemia/lymphoma or Burkitt leukemia/lymphoma? Arch Pathol Lab Med. 2003; 127(10): 1340–1344.
- Tsao L, Draoua HY, Osunkwo I, et al. Mature B-cell acute lymphoblastic leukemia with t(9;11) translocation: a distinct subset of B-cell acute lymphoblastic leukemia. Mod Pathol. 2004; 17(7): 832–839.
- Blin N, Méchinaud F, Talmant P, et al. Mature B-cell lymphoblastic leukemia with MLL rearrangement: an uncommon and distinct subset of childhood acute leukemia. Leukemia. 2008; 22(5): 1056–1059.
- Dworzak MN, Fritsch G, Buchinger P, et al. Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood. Blood. 1994; 83(2): 415–425.
- Zuurbier L, Gutierrez A, Mullighan CG, et al. Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors. Haematologica. 2014; 99(1): 94–102.
- Ratei R, Karawajew L, Lacombe F, et al. European Working Group of Clinical Cell Analysis. Discriminant function analysis as decision support system for the diagnosis of acute leukemia with a minimal four color screening panel and multiparameter flow cytometry immunophenotyping. Leukemia. 2007; 21(6): 1204–1211.
